This invention relates to an apparatus for low temperature processing requiring sterilization and methods therefor. More particularly, this invention relates to an apparatus (and methods therefor) using halogenated organic fluids for heat transfer in low temperature processes requiring high temperature (e.g., steam) sterilization.
Low temperature processing can generally be described as a dehydration, a chemical reaction, a biological reaction, etc. which occurs in a vessel or chamber at temperatures ranging from about xe2x88x92150xc2x0 C. to about 0xc2x0 C. The low temperature processes of particular interest in the present invention occur in a vessel or chamber which requires sterilization (or a high temperature process) at the end of the low temperature processing. Examples of such chambers include, but are not limited to, a vacuum chamber from freeze drying and a chemical or biological reactor.
Freeze drying can generally be described as a process of dehydration or of separating water from matter (e.g., biological matter or chemical matter). A product containing biological or chemical matter is frozen and then subjected to a high vacuum. The water vaporizes without melting (sublimes) leaving behind non-water components.
Generally, freeze drying requires at least four components: a vacuum chamber, a condenser, a pump, and a means for providing the heat of sublimation to the product being dried. The vacuum chamber typically contains a series of thin stainless steel shelves. Product, for example in containers, is placed upon these shelves. The condenser is used to remove the sublimed water vapor. The pump is typically a high powered vacuum pump.
A freeze drying system generally comprises other components such as a means for heat transfer. This heat transfer means may comprise a means for heating and a means for cooling. The freeze drying system typically comprises a sterilization process, especially for pharmaceutical applications.
Freeze drying systems operate over a range of temperatures, but in general the product is completely frozen prior to dehydration. The freezing point of the product may be well below the freezing point of water. For example, the freezing point of the product may be as low as about xe2x88x9250xc2x0 C. or the operating temperature may be as low as about xe2x88x9250xc2x0 C.
If sterilization is desired, the freeze drying system may also operate at temperatures around about 120xc2x0 C. to about 130xc2x0 C. (i.e., the temperature for high pressure saturated steam which is often used for sterilization).
During dehydration, a heat-transfer fluid is pumped through passages in the shelves of the vacuum chamber providing the heat of sublimation to the product being dried. Following drying, the product is removed from the container and the vacuum chamber may then be sterilized. As discussed, typically a high temperature steam (120xc2x0 C. to 130xc2x0 C.) is used for this sterilization process. If the heat-transfer fluid in the passages boils during this sterilization process, the system pressure may rise to a level where the shelves (which are typically thin to ensure adequate heat transfer) are damaged. Thus, selection of heat-transfer fluid is critical.
Heat-transfer fluids used in such applications typically have low viscosities at lower temperatures (i.e., xe2x88x9250xc2x0 C. for the shelves and xe2x88x9280xc2x0 C. for the condenser system), but are readily maintained in the liquid phase at the highest operating temperature for the system (which is typically during sterilization). Desirable heat-transfer fluids for freeze drying applications are also non-corrosive, non-toxic, and non-flammable.
Polydimethylsiloxanes (silicone oils) have a suitably wide liquid range and are often used in freeze drying. The average molecular weight of the silicone oil can be selected such that it functions well at temperatures as low as xe2x88x9280xc2x0 C. At this temperature, the heat-transfer fluid may be pumped through passages in the shelves where the product is being dried. Such a silicone oil has a boiling point significantly above 130xc2x0 C., thus the passages may be kept full of heat-transfer fluid without the danger of the heat-transfer fluid boiling and causing elevated system pressure. Silicone oils seem to be ideally suited for this type of application. However, they are flammable. There have been instances of silicone oil fires and such fires can cost millions of dollars as well as injury.
As is the case with freeze drying, during low temperature chemical or biological processes, the heat-transfer fluid preferably has good low temperature heat transfer characteristics. Typically, the heat-transfer fluid is pumped through a reactor jacket for heating, cooling, or temperature control. For ease of handling and safety, preferably this fluid is non-toxic and non-flammable. The heat-transfer fluid has similar temperature constraints (i.e., suitable at low temperature processing temperatures and at high temperature sterilization temperatures).
Halogenated organic compounds, such as perfluorocarbons (PFCs), perfluoropolyethers (PFPEs), hydrofluorocarbons (HFCs), chlorofluorocarbons (CFCs), hydrochlorofluorocarbons (HCFCs), hydrofluoroethers (HFEs), hydrohalofluoroethers (HHFEs), hydrochlorocarbons (HCCs), hydrobromocarbons (HBCs), perfluoroalkyl iodides (PFIs), perfluoroolefins (PFOs), and fluorinated compounds containing at least one aromatic moiety, or mixtures thereof are generally non-toxic and non-flammable. The lower molecular weight compounds tend to have good low temperature heat transfer properties. Additionally, halogenated organic compounds are non-corrosive and very thermally stable.
However, in conventional designs these halogenated organic compounds tend not to be viable candidates as heat-transfer fluids because either their boiling points are too low (leading to excessive system pressure at high temperatures) or their freezing points are too high (leading to freeze up or high viscosity at low temperatures). Candidates, for example, that are liquid at 130xc2x0 C. or which have acceptable vapor pressures at this temperature tend to be solid or very viscous at xe2x88x9280xc2x0 C. and thus cannot be used. Similarly, candidates, for example, that may work well at xe2x88x9280xc2x0 C. tend to have lower boiling points which result in excessive vapor pressures that would prevent their use at 130xc2x0 C. Typically, these fluids are not used in conventional designs because to maintain the fluid in a liquid state throughout the system/apparatus and throughout the operating temperature range, the system is typically pressurized above the fluid saturation pressure using a compressed gas such as air or nitrogen. This pressure compromises certain components in the apparatus unless they are built to more rigorous design codes which adds cost and may affect performance.
Thus, the need exists for an apparatus which allows volatile halogenated organic compounds having good heat transfer properties at low temperatures, non-corrosivity, non-flammability, low toxicity, etc. to be utilized in low temperature processes requiring high temperature sterilization.
The present invention provides an apparatus for low temperature processing where the chamber requires sterilization which allows a volatile halogenated organic compound to be effectively used as a heat-transfer fluid. The apparatus of the present invention allows for heat-transfer fluids to be used which have a boiling point of less than about 120xc2x0 C. Thus, fluids having otherwise desirable traits can be utilized.
The present invention provides an apparatus for low temperature processing and high temperature sterilization comprising: a product; a heat-transfer fluid having a saturation temperature at a system pressure below the sterilization temperature; a chamber requiring sterilization comprising one or more passageway(s) for said heat-transfer fluid wherein said heat-transfer fluid enters and exits said passageway(s) at the lower portion of said chamber; a pump in fluid connection with said passageway(s); and an expansion device sized to accommodate the equivalent volume of heat-transfer fluid in said passageway(s) and thermal expansion of the heat-transfer fluid; wherein said expansion device is in fluid connection with said pump and said passageway(s); and wherein during the chamber sterilization a portion of the heat-transfer fluid vaporizes causing the non-vaporized portion of heat-transfer fluid to evacuate the passageway(s) in the chamber in such a way that a liquid-vapor interface forms outside of the passageway(s).
The apparatus of the present invention may further comprise an expansion device comprising a membrane to separate the heat-transfer fluid from the pressurization gas (e.g., ambient air).
Another embodiment of the present invention is an apparatus for low temperature processing and high temperature sterilization comprising: a product; a heat-transfer fluid having a saturated temperature at a system pressure below the sterilization temperature; a chamber requiring sterilization comprising one or more passageway(s) for said heat-transfer fluid; a pump in fluid connection with said passageway(s); and an expansion device sized to accommodate the equivalent volume of heat-transfer fluid in the passageway(s) and thermal expansion of the heat-transfer fluid; wherein prior to sterilization, the heat-transfer fluid is substantially evacuated from the passageway(s) by flowing into the expansion device.
Yet another embodiment of the present invention is a method of sterilizing a low temperature processing chamber comprising the steps of: (a) providing a chamber comprising one or more passageway(s); (b) providing heat-transfer fluid having a saturation temperature at a system pressure below the sterilization temperature in said passageway(s); (c) providing a means for sterilization; (d) allowing energy to flow from said means for sterilization to said heat-transfer fluid such that some of said heat-transfer fluid vaporizes; (e) after step (d), said vaporized heat-transfer fluid causing the non-vaporized heat-transfer fluid to flow to an expansion device in fluid connection with said passageways and having sufficient volume to accommodate said non-vaporized heat-transfer fluid; (f) after step (e), causing a liquid-vapor interface to form outside of said passageway(s); (g) completing the sterilization of the chamber; (h) allowing the chamber to cool; and (i) allowing the heat-transfer fluid to re-fill the passageway(s).
Another embodiment of the present invention is a method of sterilizing a low temperature processing chamber comprising the steps of: (a) providing a chamber comprising one or more passageway(s); (b) providing heat-transfer fluid having a saturation temperature at a system pressure below the sterilization temperature in said passageway(s); (c) causing said heat-transfer to leave said passageway(s) and to flow to an expansion device in fluid connection with said passageway(s) and having sufficient volume to accommodate said heat-transfer fluid from said passageway(s); (d) interrupting said fluid connection between said passageway(s)and said expansion device; (e) providing a means for sterilization; (f) sterilizing said chamber; (g) completing said sterilization; (h) allowing said chamber to cool; and (i) allowing said heat-transfer fluid to re-fill said passageway(s).
The present invention provides for either passive or actively controlled evacuation of the passageway(s). The passively-controlled system in particular may be readily retrofitted into existing systems.